The outpatient clinic provides a "well state" patient population for genetic and pharmacologic studies of persons with Bipolar (manic-depressive disorders and Unipolar (major depressive) disorders. Such a "well state" population is crucial in identifying biochemical, pharmacologic, or physiologic abnormalities which are present in persons vulnerable to affective disorder, and which may serve as genetic markers to affective illness. The clinic also provides a resource for studies of phenomenology of manic-depressive illness and treatment response to medications. Studies of cholinergic sensitivity in Bipolar patients and relatives are continuing. We have tested mood and hormonal response to arecoline in euthymic patients and normal controls. This data is now being analyzed. We are also testing trihexphyenidyl, an anticholinergic agent, as an anti-depressant in Bipolar patients. Four patients have been started in this protocol.